A Philippon

Université René Descartes - Paris 5, Lutetia Parisorum, Île-de-France, France

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Publications (157)438.49 Total impact

  • A. Philippon
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    ABSTRACT: Les bêta-lactamases à spectre élargi ou étendu (BLSE) ont émergé peu de temps après l’introduction des céphalosporines de troisième génération (C3G). Il s’agissait dans un premier temps (1985) de pénicillinases connues (TEM/SHV) ayant modifié leur affinité pour les bêta-lactamines dont les C3G par mutation(s) (par exemple : positions 104, 164, 238, 240 pour les enzymes de type TEM). Quelques années plus tard, cette résistance, en particulier aux C3G, était en relation avec de nouvelles BLSE telles BES-1, CTX-M-1, PER-1, SFO-1, TLA-1, Toho-1, VEB-1... Cette émergence de nouveaux types ne devait plus s’arrêter avec les deux dernières : BEL-1, PME-1. Néanmoins, une véritable pandémie mondiale est maintenant observée avec la diffusion préférentielle des types CTX-M dont CTX-M-15, en particulier en milieu communautaire chez des souches de E. coli d’origine urinaire. Plus récemment, a été identifié un clone pandémique (025b:H4, ST131) pouvant associer la multirésistance aux antibiotiques à la virulence. Les BLSE se définissent comme des enzymes de la classe A transférables, donc sensibles aux inhibiteurs enzymatiques (acide clavulanique). En pratique de laboratoire, leur détection est simple d’autant que les concentrations c et C ont été récemment abaissées (≤ 1 mg/L et > 2 ou 4 mg/L) en combinant un test de synergie. Leur identification précise ne peut être que moléculaire et donc, réservée à des laboratoires spécialisés.
    Immuno-analyse & Biologie Spécialisée 10/2013; 28(s 5–6):287–296. DOI:10.1016/j.immbio.2013.04.006 · 0.11 Impact Factor
  • A Philippon
    Pathologie Biologie 10/2012; 60(5):269. DOI:10.1016/j.patbio.2012.10.001 · 1.07 Impact Factor
  • A Philippon · G Arlet
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    ABSTRACT: Four susceptibility patterns of wild types of enterobacteria against old beta-lactams including aminopenicillins, carboxypenicillins and first-generation cephalosporins were individualized during the 1980s : susceptible, penicillinase low level, cephalosporinase and a combination of penicillinase and cephalosporinase. Such indirect detection of a mechanism of resistance allowed an interpretative reading for this class of antibiotics. At the present time, seven susceptibility patterns were proposed for this family of gram negative bacilli. Nevertheless, an analysis of results in terms of MICs and diameters of inhibition zone sizes of the main bacterial species of enterobacteria, mainly obtained from the databank of European Committee on Antimicrobial Susceptibility Testing (EUCAST), compared to that observed when overproducing strains were isolated in vivo and in vitro and to the type of beta-lactamase identified and their amino acid sequences conducted to a proposal of five susceptibility patterns. The fifth wild type individualized in several enterobacteria since 2005 is related to the synthesis of various chromosomal extended-spectrum beta-lactamases (ESBL) which hydrolyze many beta-lactams including oxyimino-cephalosporins such as ceftriaxone or cefotaxime. Their expression in a wild strain is characteristic and conducted to our interest for their role as progenitors of the transferable CTM-M types. Otherwise, a medical biologist must consider the possibility of selection of a mutant with a chromosomal overproduced beta-lactamase. But within the same beta-lactam susceptibility pattern such as for Klebsiella pneumoniae and K. oxytoca or Citrobacter amalonaticus, the spectrum of inactivation will be highly variable according to the type of enzyme overproduced. Finally, a nice synergy observed between clavulanic acid and cefotaxime or ceftriaxone or even aztreonam does not mean anytime a transferable ESBL. In some cases according to the result of enterobacterial identification, the epidemiological impact will be very low, because without multidrug resistance (MDR).
    Pathologie Biologie 01/2012; 60(2):112-26. DOI:10.1016/j.patbio.2011.12.002 · 1.07 Impact Factor
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    ABSTRACT: Lactobacillus urinary tract infection (UTI) seems exceptionally reported. Nevertheless, with the introduction of a chromogenic medium UriSelect 4, eight cases of UTI in old women (mean of 81.2 years) mediated by Lactobacillus delbrueckii identified by DNA sequencing were reported between 2007 and 2009.
    Pathologie Biologie 06/2010; 60(2):140-2. DOI:10.1016/j.patbio.2010.04.003 · 1.07 Impact Factor
  • Source
    A Doloy · C Verdet · V Gautier · D Decré · E Ronco · A Hammami · A Philippon · G Arlet
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    ABSTRACT: We studied the genetic organization of bla(ACC-1) in 14 isolates of Enterobacteriaceae from France, Tunisia, and Germany. In a common ancestor, ISEcp1 was likely involved in the mobilization of this gene from the Hafnia alvei chromosome to a plasmid. Other genetic events involving insertion sequences (particularly IS26), transposons (particularly Tn1696), or sulI-type integrons have occurred, leading to complex genetic environments.
    Antimicrobial Agents and Chemotherapy 01/2007; 50(12):4177-81. DOI:10.1128/AAC.00619-06 · 4.45 Impact Factor
  • A. Philippon · G. Paul · M. Barthelemy · R. Labia · P. Nevot · G. Fournier · L. Gilly
    FEMS Microbiology Letters 03/2006; 8(4):191 - 194. DOI:10.1111/j.1574-6968.1980.tb05077.x · 2.72 Impact Factor
  • A Philippon · G Arlet
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    ABSTRACT: The acquired resistance against the wide-spectrum and highly stable beta-lactams including third-generation cephalosporins (3GC) and carbapenems is constinuously increasing and widespead with the discovery of various plasmid-encoded, or genes cassette or integrons coding for a novel beta-lactamase, always a major mechanism of resistance. To explain resistance against 3GC, with the continuing story with TEM and SHV mutated enzymes, several types of ESBL (class A) emerge the CTX-M type, at least CTX-M-40, but also other non predominant types intitled BES, GES, PLA, PER, VEB. The wider resistance including 3GC, cephamycins and beta-lactamase inhibitor is correlated to synthesis of transferable cephalosporinases (class C) usually located in the chromosome but mobilized from Enterobacter spp., Citrobacter freundii, Hafnia alvei, Morganella morganii, Aeromonas caviae. Such genes encoded the following types: ACC-1, ACT-1, CFE-1, CMY group, DHA-1, FOX group, MIR-1, MOX-1. Finally the resistance against carbapemens e.g. imipenem originally restricted to Pseudomonas aeruginosa, then to Acinetobacter baumannii and finally to enterobacteria is related to production of novel enzymes (classes B, D and A) denominated IMP, VIM SME, GIM, OXA, KPC. A striking exemple of evolution towards more and more resistance is given by Salmonella, even from animal origins, a great threat fo public health. So far it appears necessary to perform molecular approaches to identify such enzymatic production. Finally because the absence of real new drugs, the discovery of some progenitors of the gene beta-lactamase, a strict control of beta-lactam antibiotics must be provide not only in medecine or veterinary field but also in agriculture, including aquaculture for example.
    Annales de biologie clinique 01/2006; 64(1):37-51. · 0.42 Impact Factor
  • A. Philippon · G. Arlet
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    ABSTRACT: Among gram-negative bacteria, the role of β-lactamases for natural and acquired resistance is essential and more and more complex. Numerous corresponding genes located in chromosome, plasmid, integron or CR (common region) were cloned and sequenced showing a very high diversity among this type of inactivating enzymes. A lot of genetic answers were developed by bacteria after introduction of new drugs such as β-lactam antibiotics. Such adaptability of bacterial world must lead to limit the abuse of prescriptions and a better use of drugs.
    Antibiotiques 12/2005; 7(4):247-259. DOI:10.1016/S1294-5501(05)80458-3
  • Source
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    ABSTRACT: We analyzed 19 clinical isolates of the family Enterobacteriaceae (16 Escherichia coli isolates and 3 Klebsiella pneumoniae isolates) collected from four different hospitals in Paris, France, from 2000 to 2002. These strains had a particular extended-spectrum cephalosporin resistance profile characterized by a higher level of resistance to cefotaxime and aztreonam than to ceftazidime. The bla(CTX-M) genes encoding these beta-lactamases were involved in this resistance, with a predominance of bla(CTX-M-15). Ten of the 19 isolates produced both TEM-1- and CTX-M-type enzymes. One strain (E. coli TN13) expressed CMY-2, TEM-1, and CTX-M-14. bla(CTX-M) genes were found on large plasmids. In 15 cases the same insertion sequence, ISEcp1, was located upstream of the 5' end of the bla(CTX-M) gene. In one case we identified an insertion sequence designated IS26. Examination of the other three bla(CTX-M) genes by cloning, sequencing, and PCR analysis revealed the presence of a complex sul1-type integron that includes open reading frame ORF513, which carries the bla gene and the surrounding DNA. Five isolates had the same plasmid DNA fingerprint, suggesting clonal dissemination of CTX-M-15-producing strains in the Paris area.
    Antimicrobial Agents and Chemotherapy 05/2004; 48(4):1249-55. DOI:10.1128/AAC.48.4.1249-1255.2004 · 4.45 Impact Factor
  • G. Arlet · A. Philippon
    Revue Française des Laboratoires 01/2003; 2003(352).
  • L. Prots · A. Philippon
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    ABSTRACT: Résumé Depuis plus d’une décennie, le séquençage de certains gènes bactériens est considéré comme la méthode la plus performante et la plus rapide des études taxonomiques avec la reconsidération des grands groupes et genres bactériens. L’autre critère génétique de la taxonomie est celui de l’hybridation entre ADN.
    Bio Tribune Magazine 01/2003; 8(1):30-33. DOI:10.1007/BF03010256
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    ABSTRACT: Because a multiresistant K. pneumoniae outbreak detected in an intensive care unit of a parisian hospital, combined to the production of the plasmid-encoded cephalosporinase ACC-1, a probable importation via a patient was suggested from another country (Tunisia). The investigation was conducted to examine 35 clinical strains of enterobacteria resistant to ceftazidime without synergy towards Augmentin. Other test of synergy with two inhibitors, BRL 42715, Ro 48-5545 was performed by diffusion method and deposit of 10 micrograms of inhibitor on disks containing ceftazidime, cefoxitin and cefotetan. Synergies were obtained suggesting a probable production of ACC-1 type among six isolates of K. pneumoniae (two), Proteus mirabilis (one) and Salmonella (three) issued from different units. The isoelectric focusing on gel revealed at least one band of beta-lactamase activity at 7.8 but also demonstrated the simultaneous production of several probable beta-lactamases including TEM-type, SHV-2 and ACC-1 among S. enterica ser. Livingstone. The PCR of the gene blaacc-1 was positive. The sequencing (1160 pb) of two products showed high identity (99-100%) with the gene blaacc-1 deposited in 1999. Finally the ACC-1 type reported in Tunisia was probably imported in France via a patient. Because a simultaneous synthesis of ESBL and ACC-1 type, its presence may be invisible and need more investigation.
    Pathologie Biologie 03/2002; 50(1):7-11. · 1.07 Impact Factor
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    ABSTRACT: Because a multiresistant K. pneumoniae outbreak detected in an intensive care unit of a parisian hospital, combined to the production of the plasmid-encoded cephalosporinase ACC-1, a probable importation via a patient was suggested from another country (Tunisia). The investigation was conducted to examine 35 clinical strains of enterobacteria resistant to ceftazidime without synergy towards Augmentin®. Other test of synergy with two inhibitors, BRL 42715, Ro 48-5545 was performed by diffusion method and deposit of 10 μg of inhibitor on disks containing ceftazidime, cefoxitin and cefotetan. Synergies were obtained suggesting a probable production of ACC-1 type among six isolates of K. pneumoniae (two), Proteus mirabilis (one) and Salmonella (three) issued from different units. The isoelectric focusing on gel revealed at least one band of β-lactamase activity at 7.8 but also demonstrated the simultaneous production of several probable β-lactamases including TEM-type, SHV-2 and ACC-1 among S. enterica ser. Livingstone. The PCR of the gene blaacc-1 was positive. The sequencing (1160 pb) of two products showed high identity (99–100%) with the gene blaacc-1 deposited in 1999. Finally the ACC-1 type reported in Tunisia was probably imported in France via a patient. Because a simultaneous synthesis of ESBL and ACC-1 type, its presence may be invisible and need more investigation.
    Pathologie Biologie 01/2002; 50(1):7-11. DOI:10.1016/S0369-8114(01)00260-7 · 1.07 Impact Factor
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    G Arlet · D Nadjar · J L Herrmann · J L Donay · P H Lagrange · A Philippon
    Antimicrobial Agents and Chemotherapy 11/2001; 45(10):2971-2. · 4.45 Impact Factor
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    Antimicrobial Agents and Chemotherapy 10/2001; 45(10):2971-2972. DOI:10.1128/AAC.45.10.2971-2972.2001 · 4.45 Impact Factor
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    ABSTRACT: A multicenter study was carried out to evaluate the performance of a new commercial automated system in comparison with that of the reference agar dilution method. Ten clinical microbiology laboratories tested a collection of 61 strains of gram-negative bacilli (49 Enterobacteriaceae and 12 Pseudomonas aeruginosa), and 6 other laboratories tested a collection of 55 strains of gram-positive cocci (10 enterococci and 45 staphylococci) against 10-20 antimicrobial agents. The strains were selected on the basis that they harbored challenging and characterized mechanisms of resistance. In comparison with the agar reference method, the automated system gave an overall essential agreement (+/-1 dilution) of 94.5%, 93.5%, and 97% for the gram-negative bacilli, enterococci, and staphylococci, respectively. According to the interpretive standards of the National Committee for Clinical Laboratory Standards, the category agreement ranged from 96 to 96.4% for the three sets of organisms. The accuracy of the automated system, as determined by the kappa test, ranged from 0.80 to 0.88, reflecting an almost perfect agreement with the reference technique. Very major, major, and minor errors obtained with the automated system were 0.3%, 2.9%, and 6.6% for gram-negative bacilli, 3.4%, 0%, and 5% for enterococci, and 1%, 1.6%, and 2.7% for staphylococci, respectively. The high rate of very major errors in enterococci was mostly due to a single strain of multidrug-resistant Enterococcus faecium, which was found susceptible to several antibiotics in a majority of participant laboratories. The use of a heavy inoculum and of a broth test medium by the automated system might account for a better expression of certain resistance mechanisms, including beta-lactamases, as compared to the agar dilution reference method. The interlaboratory reproducibility was acceptable, as shown by the narrow dispersion of MICs and by the results of quality control.
    European Journal of Clinical Microbiology 10/2001; 20(9):626-35. DOI:10.1007/s100960100574 · 2.67 Impact Factor
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    D Nadjar · R Labia · C Cerceau · C Bizet · A Philippon · G Arlet
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    ABSTRACT: Ochrobactrum anthropi, formerly known as CDC group Vd, is an oxidase-producing, gram-negative, obligately aerobic, non-lactose-fermenting bacillus of low virulence that occasionally causes human infections. It is highly resistant to all beta-lactams except imipenem. A clinical isolate, SLO74, and six reference strains were tested. MICs of penicillins, aztreonam, and most cephalosporins tested, including cefotaxime and ceftazidime, were >128 microg/ml and of cefepime were 64 to >128 microg/ml. Clavulanic acid was ineffective and tazobactam had a weak effect in association with piperacillin. Two genes, ampR and ampC, were cloned by inserting restriction fragments of genomic DNA from the clinical strain O. anthropi SLO74 into pBK-CMV to give the recombinant plasmid pBK-OA1. The pattern of resistance to beta-lactams of this clone was similar to that of the parental strain, except for its resistance to cefepime (MIC, 0.5 ,micro/ml). The deduced amino acid sequence of the AmpC beta-lactamase (pI, 8.9) was only 41 to 52% identical to the sequence of other chromosomally encoded and plasmid-encoded class C beta-lactamases. The kinetic properties of this beta-lactamase were typical for this class of beta-lactamases. Upstream from the ampC gene, the ampR gene encodes a protein with a sequence that is 46 to 62% identical to those of other AmpR proteins and with an amino-terminal DNA-binding domain typical of transcriptional activators of the Lys-R family. The deduced amino acid sequences of the ampC genes of the six reference strains were 96 to 99% identical to the sequence of the clinical strain. The beta-lactamase characterized from strain SLO74 was named OCH-1 (gene, bla(OCH-I)).
    Antimicrobial Agents and Chemotherapy 09/2001; 45(8):2324-30. DOI:10.1128/AAC.45.8.2324-2330.2001 · 4.45 Impact Factor
  • Pathologie Biologie 12/2000; 48(9):832-71. · 1.07 Impact Factor
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    ABSTRACT: Fifty-two strains of Klebsiella pneumoniae producing an AmpC-type plasmid-mediated beta-lactamase were isolated from 13 patients in the same intensive care unit between March 1998 and February 1999. These strains were resistant to ceftazidime, cefotaxime and ceftriaxone, but susceptible to cefoxitin, cefepime and aztreonam. Plasmid content and genomic DNA restriction pattern analysis suggested dissemination of a single clone. Two beta-lactamases were identified, TEM-1 and ACC-1. We used internal bla(ACC-1) primers, to sequence PCR products obtained from two unrelated strains of Hafnia alvei. Our results show that the ACC-1 beta-lactamase was derived from the chromosome-encoded AmpC-type enzyme of H. alvei.
    FEMS Microbiology Letters 07/2000; 187(1):35-40. · 2.72 Impact Factor
  • Médecine et Maladies Infectieuses 01/2000; 30(1). · 0.91 Impact Factor

Publication Stats

3k Citations
438.49 Total Impact Points

Institutions

  • 1984–2013
    • Université René Descartes - Paris 5
      • Faculty of medicine
      Lutetia Parisorum, Île-de-France, France
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 2007
    • Pierre and Marie Curie University - Paris 6
      • Faculté de médecine Pierre et Marie Curie
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 1996
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1995
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1988–1993
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
    • Muséum National d'Histoire Naturelle
      Lutetia Parisorum, Île-de-France, France
  • 1991
    • CHRU de Strasbourg
      Strasburg, Alsace, France
  • 1989–1991
    • Hôpital Raymond-Poincaré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Île-de-France, France
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1988–1990
    • Hôpital Charles-Nicolle
      Tunis-Ville, Tūnis, Tunisia